PROJECT SUMMARY The vaginal microbiota is thought to play a major role in preventing Sexually Transmitted Infections (STIs) through ecological competition, lactic acid and target-specific bacteriocins production by Lactobacillus species. A condition known as bacterial vaginosis (BV) characterized by the depletion of Lactobacillus spp. and an overabundance of anaerobic bacteria has been shown to be associated with acquisition of STIs including HSV- 2 and HIV-1. Chlamydia trachomatis (Ct) is an obligate intracellular bacterial pathogen associated with cervicitis, pelvic inflammatory disease, and subsequent tubal factor infertility and ectopic pregnancy. It is the most common bacterial STI worldwide, including in the United States. Epidemiological data suggest that the incidence of this disease has increased recently despite efforts to prevent it, which motivates the search for vaccine candidates and updates to current recommendations for Ct screening. The long-term goal of this research is to leverage biological and epidemiological data to adapt strategies for Ct control by integrating these data types. Our hypothesis is that the composition of the vaginal microbiota, and potentially its disruption, could lead to an increased susceptibility to Ct infection, independent of the effect immunogenetics may have on this relationship. If such a role could be highlighted, a change to the treatment and prevention guidelines for Ct and STI in general would be warranted. However, modification to the current recommendations for Ct screening, prevention and treatment would need to be supported by information on the natural history of Ct infection. Therefore, the objective of this project is to study the role of the vaginal microbiota in Ct acquisition and clinical presentation in a unique and already established cohort of young women prospectively followed in France. A multidisciplinary international research network has been assembled to answer these questions by focusing on two specific aims: 1) Characterize the vaginal microbiota composition, abundance and dynamics over 2 years, and the frequency of a set of immunogenetic biomarkers in a cohort of 18-24 years old women; 2) Model the interactions between the vaginal microbiota, immunogenetic factors and C. trachomatis infection using a cohort of 18-24 years old women prospectively followed. In the first aim, we will characterize the vaginal microbiota (composition and abundance) of samples from 300 women prospectively followed at four time points. We will then evaluate under the second aim the independent effects of vaginal microbiota composition and immunogenetic biomarkers on susceptibility to Ct infection as well as presence of symptoms, in order to build host-pathogen-microbiota interaction models. This research is novel in that the role of the vaginal microbiota composition in the susceptibility to Ct infection has never been studied in a large-scale prospective cohort. Its innovative potential lies in the use of novel molecular methods that allow us to refine our approach to ?health? and ?disease? by integrating individual predisposition to STIs, thus leading the way for personalized medicine.